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161.
Shashi P. Singh Hitendra S. Chand Sravanthi Gundavarapu Ali Imran Saeed Raymond J. Langley Yohannes Tesfaigzi Neerad C. Mishra Mohan L. Sopori 《PloS one》2015,10(9)
Rationale
Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1α that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1α.Methods
Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined.Results
Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-κB, HIF-1α, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine.Conclusions
Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1α, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1α pathway. 相似文献162.
163.
Alok Ranjan Singh Shweta Joshi Rahul Arya Arvind Mohan Kayastha Jitendra Kumar Saxena 《European biophysics journal : EBJ》2010,39(2):289-297
Guanidine hydrochloride and urea-induced unfolding of B. malayi hexokinase (BmHk), a tetrameric protein, was examined in detail by using various optical spectroscopic techniques, enzymatic
activity measurements, and size-exclusion chromatography. The equilibrium unfolding of BmHk by guanidine hydrochloride (GdmCl)
and urea proceeded through stabilization of several unique oligomeric intermediates. In the presence of low concentrations
of GdmCl, stabilization of an enzymatically active folded dimer of BmHk was observed. However an enzymatically inactive dimer
of BmHk was observed for urea-treated BmHk. This is the first report of an enzymatically active dimer of hexokinase from any
human filarial parasite. Furthermore, although complete recovery of the native enzyme was observed on refolding of BmHk samples
denatured by use of low concentrations of GdmCl or urea, no recovery of the native enzyme was observed for BmHk samples denatured
by use of high concentrations of GdmCl or urea. 相似文献
164.
Tubulin polymerization promoting protein 3 (TPPP3), a member of the TPPP family, can induce tubulin polymerization and microtubule bundling. Previously, it has been shown that TPPP3 plays an important role in cell proliferation. Depletion of TPPP3 by microRNA-based RNA interference (RNAi) inhibits cell growth, arrests cell cycles, and causes mitotic abnormalities in HeLa cells. In the present study, we knocked down TPPP3 in Lewis lung carcinoma (LLC) cells with the same RNAi construct, and observed a retarded tumor cell growth in vitro. Furthermore, C57BL/6 mice that received subcutaneously injected LLC cells in which TPPP3 was knocked down showed a pronounced reduction in tumor progression. The migration/invasion activity of TPPP3-knockdown LLC cells was significantly suppressed in a transwell chamber migration assay. When these cells were injected into the tail veins of C57BL/6 mice, they exhibited milder lung metastasis compared with control tumor cells. Taken together, these findings suggested that the TPPP3 gene played an important role in tumorigenesis and metastasis, and it could potentially become a novel target for cancer therapy. 相似文献
165.
Archana Aggarwal Man Mohan Misro Ankur Maheshwari Neeta Sehgal Deoki Nandan 《Molecular reproduction and development》2010,77(10):900-909
We have earlier reported that following persistent stimulation with hCG, oxidative stress‐induced apoptosis in rat Leydig cells was mainly achieved through the extrinsic pathway. In the present study, the role of N‐acetylcysteine (NAC) in counteracting the oxidative stress and the mechanisms of inhibition of apoptosis under such conditions were investigated. NAC (1 mM) intervention with repeated hCG stimulation (50 ng/ml, four times, each with 30 min challenge) prevented the decline in Leydig cell viability and the rise in lipid peroxidation and reactive oxygen species. Simultaneously, the activities of the enzymes glutathione‐S‐transferase, catalase, superoxide dismutase and the intracellular glutathione and antioxidant capacity of the treated cells improved significantly. Apoptotic markers Fas, FasL, and caspase‐8, up‐regulated following repeated hCG exposure, were significantly down‐regulated following NAC co‐incubation. While Bcl‐2 expression was fully restored, Bax and caspase‐9 remained unchanged. NAC treatment induced down‐regulation of upstream JNK/pJNK and down‐stream caspase‐3 in the target cells. Taken together, the above findings indicate that NAC counteracted the oxidative stress in Leydig cells induced as a result of repeated hCG stimulation, and inhibited apoptosis by mainly regulating the extrinsic and JNK pathways of metazoan apoptosis. Mol. Reprod. Dev. 77:900–909, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
166.
Peter Beemiller Youxin Zhang Suresh Mohan Erik Levinsohn Isabella Gaeta Adam D. Hoppe Joel A. Swanson 《Molecular biology of the cell》2010,21(3):470-480
Fcγ Receptor (FcR)-mediated phagocytosis by macrophages requires phosphatidylinositol 3-kinase (PI3K) and activation of the Rho-family GTPases Cdc42 and Rac1. Cdc42 is activated at the advancing edge of the phagocytic cup, where actin is concentrated, and is deactivated at the base of the cup. The timing of 3′ phosphoinositide (3′PI) concentration changes in cup membranes suggests a role for 3′PIs in deactivation of Cdc42. This study examined the relationships between PI3K and the patterns of Rho-family GTPase signaling during phagosome formation. Inhibition of PI3K resulted in persistently active Cdc42 and Rac1, but not Rac2, in stalled phagocytic cups. Patterns of 3′PIs and Rho-family GTPase activities during phagocytosis of 5- and 2-μm-diameter microspheres indicated similar underlying mechanisms despite particle size–dependent sensitivities to PI3K inhibition. Expression of constitutively active Cdc42(G12V) increased 3′PI concentrations in plasma membranes and small phagosomes, indicating a role for Cdc42 in PI3K activation. Cdc42(G12V) inhibited phagocytosis at a later stage than inhibition by dominant negative Cdc42(N17). Together, these studies identified a Cdc42 activation cycle organized by PI3K, in which FcR-activated Cdc42 stimulates PI3K and actin polymerization, and the subsequent increase of 3′PIs in cup membranes inactivates Cdc42 to allow actin recycling necessary for phagosome formation. 相似文献
167.
168.
Subramanian Mohan Raj Chelladurai Rathnasingh Woo-Chel Jung Edwardraja Selvakumar Sunghoon Park 《Biotechnology and Bioprocess Engineering》2010,15(1):131-138
3-Hydroxypropionic acid (3-HP), a versatile and valuable platform chemical, has diverse industrial applications; but its biological
production from glycerol is often limited by the capability of the enzyme aldehyde dehydrogenase (ALDH) to convert an intermediary
compound, 3-hydroxypropionaldehyde (3-HPA), to 3-HP. In this study, we report a new ALDH, PuuC, from Klebsiella pneumoniae DSM 2026, that efficiently converts 3-HPA to 3-HP. The identified gene puuC was cloned, expressed in Escherichia coli, purified, and characterized for its properties. The recombinant enzyme with a molecular weight of 53.8 kDa exhibited broad
substrate specificity for various aliphatic aldehydes, especially C2–C5 aldehydes. NAD+ was the preferred coenzyme for the oxidation of most aliphatic and aromatic aldehydes tested. The optimum pH and temperature
for PuuC activity were pH 8.0 and 45°C. The K
m values for 3-HPA and NAD+ were 0.48 and 0.09 mM, respectively. The activity of PuuC was enhanced in the presence of reducing agents such as 2-mercaptoethanol
or dithiothreitol, while several metal ions, particularly Hg2+, Ag+, and Cu2+ inhibited its activity. The predicted structure of PuuC indicated the presence of K191 and E194 in close proximity to the
glycine motif, suggesting that PuuC belongs to class 2 ALDHs. 相似文献
169.
170.
Jagmohan S. Negi Pramod Singh Geeta J. Nee Pant Mohan S. Maniyari Rawat H. K. Pandey 《Biological trace element research》2010,135(1-3):275-282
The present study was carried out to determine the accumulation and variation of trace elements in roots and leaves of Asparagus racemosus collected from four different altitudes in Uttarakhand, India, by atomic absorption spectroscopy. The metals investigated were Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li. The concentration level of Fe was found to be highest at an altitude of 2,250 m, whereas the level of Cu was lowest. The maximum concentrations of Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li were found to be 165.0?±?3.2, 34.0?±?0.5, 84.0?±?0.7, 2,040.0?±?0.3, 122.0?±?1.5, 745.0?±?0.3, 13,260.0?±?3.5, 6,153.0?±?1.6, and 58.0?±?3.8 mg/kg, respectively. 相似文献